Caffein and its allies form a very important group of diuretics. The urine is generally of a lower specific gravity than normal, since it contains a lesser proportion of salt and urea; but the total excretion of solids, both as regards urea, uric acid, and salts, is increased. Caffein, by exciting the medulla, produces an initial vaso-constriction of the kidneys, which tends at first to retard the flow of urine. So in recent years, other drugs have been introduced, allies of caffein, which act like it on the kidneys, but are without the stimulant action on the brain. Theobromine is such a drug. Another authority states that[258]: One of the most constant symptoms produced in man by over-doses of caffein is excessive diuresis, and experiments made upon the lower animals show that caffein acts as a diuretic not only by influencing the circulation, but also by directly affecting the secreting cells, the probabilities being in favor of the first of these theories of action. According to Schroeder, not only the water but also the solids of the urine are increased. The question whether caffein has an influence upon tissue changes and the consequent nitrogenous elimination can not be considered as distinctly answered, though the most probable conclusion is that the action of caffein upon urea elimination and upon general nutrition is not direct or pronounced. While the therapeutic dose of caffein is broken up in the body with the formation of methylxanthin, which escapes with the urine, the toxic dose is at least in part eliminated by the kidney unchanged. The metabolism of the methyl purins, of which group caffein is a member, appears to vary with the quantity ingested. The manner in which the methyl group is liberated by the cell protoplasm is said[259] to determine the amount of stimulus which the tissues receive from these substances. The xanthin group is almost without any excitatory action, and its metabolic end products are constant. Perhaps the variation in the excretions of unchanged methylpurins is dependent upon the amount of total reactive energy they invoke.